Enhancement of nk cytotoxicity, antimetastasis and elongation effect of survival time in b16-f10 melanoma cells by oregonin

Abstract

We investigated the antitumor activity of oregonin, a diarylheptanoid derivative purified from Alnus hirsuta Turcz, Betulaceae. Oregonin is a potential novel immunomodulator, which augments the activation of natural killer (NK) cells, and thereby leads to a powerful antitumor activity. To evaluate the cytotoxicity of oregonin against tumor cells, we examined the effectiveness of NK cells and determined that oregonin could increase NK cell cytotoxicity. This was confirmed by MTT assay. In addition, the survival time of C57BL/6 mice were measured by inoculating B16-F10 melanoma cells to mice via intra muscular (i.m.) injection. Oregonin treatment after 10 hours of inoculation at 10 mg/kg dosage showed a significant extension of survival time by up to 51.32%, when compared to the control group. Moreover, oregonin significantly reduced the incidence of pulmonary metastasis, which may be developed from B16-F10 melanoma cells. These findings suggest that oregonin may be classified as a new and novel immunomodulator due to its potential antitumor activity.

Isolation of murine hepatic lymphocytes using mechanical dissection for phenotypic and functional analysis of NK1.1+cells

“…They exerted their versatile roles in the defense of pathogens like murine cytomegalovirus (MCMV) [21,22] . Several studies also reported that hepatic NK and NKT cell took part in the antimetastasis of tumor [23][24][25] . NK1.1 + cells were reported to involve in the pathogenesis of many diseases, like human immunodeficiency virus (HIV) infection and liver disease [26,27] .…”

Inhibition of activated responses in dendritic cells exposed to lipopolysaccharide and lipoteichoic acid by diarylheptanoid oregonin

“…It has been shown that oregonin reveals anti-oxidant and anti-inflammatory effects, and antitumor-promoting effect [13,14,16]. Oregonin has been shown to reveal antioxidative effect through scavenging actions on superoxide and 1,1-diphenyl-2-picrylhydrazyl radical [15].…”

Diarylheptanoid hirsutenone enhances apoptotic effect of TRAIL on epithelial ovarian carcinoma cell lines via activation of death receptor and mitochondrial pathway

“…These compounds prevent the inducible nitric oxide synthase expression and nitric oxide production in RAW264.7 macrophages treated with lipopolysaccharide [8,9,11] and attenuate lipopolysaccharide-induced expression of cyclooxygenase-2 and production of prostaglandin E and cytokines [9,13]. Oregonin increases the toxicity of natural killer cells against B16-F10 melanoma cell lines [12]. Hirsutenone has been shown to inhibit the tumor promoter 12-O-tetradecanoylphorbol-13-acetateinduced upregulation of cyclooxygenase-2 and matrix metalloproteinase-9 in human mammary epithelial MCF 10A cell lines [15].…”

“…Pharmacologically active diarylheptanoids such as oregonin and hirsutenone are isolated from Alnus hirsuta Turcz, Alnus japonica and Alnus formosana [7][8][9] and have been shown to possess anti-inflammatory and anti-tumor effects [9][10][11][12][13][14]. These compounds prevent the inducible nitric oxide synthase expression and nitric oxide production in RAW264.7 macrophages treated with lipopolysaccharide [8,9,11] and attenuate lipopolysaccharide-induced expression of cyclooxygenase-2 and production of prostaglandin E and cytokines [9,13].…”